Implementing the NHLBI Strategic Vision in the Division of - - PowerPoint PPT Presentation

Implementing the NHLBI Strategic Vision in the Division of Cardiovascular Sciences

David Goff, MD, PhD Director Division of Cardiovascular Sciences November 2020 This material represents my personal views and does not necessarily represent the official views of the NHLBI, NIH, DHHS, or US Federal Government.

Charting the Future Together: The NHLBI Strategic Vision, 2016

NHLBI Strategic Objectives

Objective 1: Normal Biology

Objective 2: Pathobiology, Onset, & Progression of HLBS diseases

Objective 3: Population Differences Objective 4: Precision Medicine Objective 5: Novel Diagnostics & Therapeutics Objective 6: Clinical & Implementation Research Objective 7: Data Science Objective 8: Workforce & Resources

• Turning discovery into cardiovascular health
• Current major initiatives map to NHLBI’s Strategic Vision
• New initiatives for strategic

investments guided by Strategic Vision, complemented by Big Goals

Division of Cardiovascular Sciences Strategic Vision Implementation

CVD in the US: Recent stagnation and enduring disparities

Sidney S, et al. BMC Cardiovasc Disord. 2017 Jul 18;17(1):192.

Sustaining DCVS Leadership with Big Goals

• Addressing social determinants of CVH and health inequities
• Enhancing resilience
• Promoting CVH and preventing CVD across the lifespan
• Eliminating hypertension-related CVD
• Reducing the burden of heart failure
• Preventing vascular dementia

Goff David, C., et al. (2019). "Implementing the National Heart, Lung, and Blood Institute’s Strategic Vision in the Division of Cardiovascular Sciences." Circ Res 124(4): 491-497.

Addressing Social Determinants of CVH Equity: DECIPHER

• Disparities Elimination through

Coordinated Interventions to Prevent and Control Heart & Lung Disease Risk

• High Burden Communities
• Geographic Region (e.g., Appalachia,

Mississippi Delta, Stroke Belt, Oklahoma to Eastern Kentucky)

• Rural or Inner-city locales
• Racial/Ethnic Groups (e.g. Blacks or African

Americans, American Indian and/or Alaska Natives)

• Low socioeconomic status
• Sex
• Creative academic-community partnerships
• Creative use of health metrics

Mensah et al. Circ Res 2018;122(2):213-230 Roth et al. JAMA. 2017;317(19):1976-1992

• DECIPHeR RCC

Stevens (U24 HL151308) University of North Carolina at Chapel Hill Coordinating Center for the DECIPHeR Network

• UG3/UH3 Awards

He (UG3 HL151309) Tulane University Community Health Worker-Led Church-Based Intervention for Eliminating Cardiovascular Health Disparities in African Americans *Brown (UG3 HL154302) UCLA Multi-ethnic Multi-level Strategies and Behavioral Economics to Eliminate Hypertension Disparities in LA County Daumit (UG3 HL154280) Johns Hopkins University Achieving Cardiovascular Health Equity in Community Mental Health: Optimizing Implementation Strategies *Kho (UG3 HL154297) Northwestern University at Chicago Community Intervention to Reduce Cardiovascular Disease in Chicago (CIRCL-Chicago) *Ogedegbe (UG3 HL151310) NYU School of Medicine Actions to Decrease Disparities in Risk and Engage in Shared Support for Blood Pressure Control (ADDRESS-BP) in Blacks Matthews (UG3 HL151302) University of Illinois at Chicago Mi QUIT CARE (Mile Square QUIT Community-Access-Referral-Expansion) Szefler (UG3 HL151297) University of Colorado Denver Reducing Asthma Attacks in Disadvantaged School Children with Asthma

DECIPHeR Awards

*Studies focused on hypertension prevention, treatment, and/or control

• Social Determinants of Health: Contributions of Early Life

Adversity to Cardiovascular Disparities in Adulthood, 2018

• https://www.nhlbi.nih.gov/events/2018/social-determinants-health-

contributions-early-life-adversity-cardiovascular

• Social Determinants of Cardiometabolic Health, Disease, and

Health Disparities: Setting an Agenda for Research, 2019

• https://www.nhlbi.nih.gov/events/2019/social-determinants-

cardiometabolic-health-disease-and-health-disparities-setting

• Harnessing Novel Data Sources and Technologies for the Study of

Social Determinants of Health in HLBS Disorders, 2020

• https://www.nhlbi.nih.gov/events/2020/harnessing-novel-data-sources-

and-technologies-study-social-determinants-health-heart

Social Determinants of CV Health Workshops

Report Out from Council/BEE Sessions on Social Determinants

• f Health, 2020

Advancing Health Equity by Addressing Health Disparities and Predict, Prevent and Preempt Disease

• Partnering with key stakeholders to engage and better understand

community needs

• Build sustainable community collaborations
• Embedding trainees/community partners into large, existing clinical

studies

• Expand opportunities for transdisciplinary research
• Engage less research-intensive institutions

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Promoting CVH and preventing CVD across the lifespan: focus initially on younger ages

11

• Challenges and opportunities for the prevention and treatment of cardiovascular disease

among young adults. 2017

• https://www.nhlbi.nih.gov/events/2017/challenges-and-opportunities-prevention-and-treatment-

cardiovascular-disease-among

• Promoting Cardiovascular Health in Early Childhood (0-5 years) and Transitions in

Childhood through Adolescence. 2018

• https://www.nhlbi.nih.gov/events/2018/promoting-cardiovascular-health-early-childhood-0-5-years-

and-transitions-childhood

• Social Determinants of Health: Contributions of Early Life Adversity to Cardiovascular

Disparities in Adulthood. 2018

• https://www.nhlbi.nih.gov/events/2018/social-determinants-health-contributions-early-life-adversity-

cardiovascular

• AHA Scientific Sessions 2019: 50x50x50 - Transforming the Cardiovascular Health of

Youth for Generations to Come

• Notice of Intent to Publish a Funding Opportunity Announcement for Early

Intervention to Promote Cardiovascular Health of Mothers and Children (ENRICH).

• https://grants.nih.gov/grants/guide/notice-files/NOT-HL-20-820.html

Promoting CVH in Childhood and Young Adults

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Early Intervention to Promote Cardiovascular Health of Mothers and Children (ENRICH) Multisite (UG3/UH3 Clinical Trial Required) and a Coordinating Center (U24 Clinical Trial Not Required)

https://grants.nih.gov/grants/guide/notice-files/NOT-HL-20-820.html Poor Intermediate Ideal Promoting CVH

Seeking applications to test the effectiveness of an implementation-ready intervention designed to determine if a cardiovascular health (CVH) promotion module delivered within the context of a home visiting program can enhance maternal and early childhood CVH and address CVH disparities in both mothers and children (0-5 years).

Topics of interest are available in this link:

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Workshop informed NOSI and secondary participation in ABCD and CHEAR/HHEAR

https://www.niehs.nih.g

• v/research/supported/

exposure/chear/index.c fm Children’s [Human] Health Exposure Analysis Resource (CHEAR/HHEAR)

Notice of Special Interest (NOSI): Understanding Factors in Infancy and Early Childhood (Birth to 24 months) That Influence Obesity Development. Notice Number: NOT-HL-19-695

Surgeon General’s Call to Action to Control Hypertension

https://www.hhs.gov/surgeongeneral/reports-and-publications/disease-prevention-wellness/hypertension-executive-summary/index.html

Testing new ways of 1. treating HTN in clinical practice (G3: Optimize Patient Care) 2. improving HTN care in clinical practice (G3: Optimize Patient Care) 3. taking HTN care to people outside clinical settings with a focus on health disparities communities (G2: Ensure That the Places Where People Live, Learn, Work, and Play Support Hypertension Control) 4. implementing evidence-based care in the community: DECIPHeR, our signature program! (G2:Ensure That the Places Where People Live, Learn, Work, and Play Support Hypertension Control ) 5. Educating the public on Heart Health (G1: Make Hypertension Control a National Priority) 6. Setting the research agenda through workshops

Programs NHLBI leads to improve hypertension control with mapping to OSG Call to Action Goals (G)

• Achieving healthy behaviors​
• Addressing root causes of obesity- and aging-related increases in BP
• Managing chronic conditions in healthcare system​s
• Creating systems of team care & simplified treatment strategies
• Enabling more effective IT resources/tools
• Evidence-based incentives for sustained organizational commitment to HTN

control

• Engaging patients​
• Addressing social determinants
• Improving adherence and expanding community engagement
• Removing barriers to control (telemedicine, home blood measurement)
• 6. Setting the research agenda:

NHLBI - CDC Workshop on HTN control, October 2020

Moving from Heart Failure to Heart Healthy

Reducing the burden of Heart Failure

• The current understanding of

HFpEF suggests chronic systemic inflammation unique from HFrEF

• Diagnostic limitations
• Lack of a single biomarker
• Underuse of stress testing
• Barriers for research
• Drug intervention trials for

ace inhibitors, ARBs, aldosterone antagonists, ARNIs have been neutral

• 6.2 M Americans with HF
• 40-50% with HFpEF
• 46% increase by 2030
• Disparities among Blacks,

LatinX

Heart Failure with Preserved Ejection Fraction (HFpEF) is a critical public health problem

Tromp J, JACC, 2018

HFpEF is a diverse clinical syndrome for which a phenotype-specific treatment strategy is necessary

128 120 149

Shah SJ, J. of Cardiovasc. Trans. Res., 2017

There are many potential therapeutic targets for HFpEF

Patel RB, Annu Rev Pharmacol Toxicol, 2019 Sanna GD, JACC: HF, 2019

HeartShare initiative

Conduct large-scale analysis of phenotypic data, images, and omics from patients with heart failure with preserved ejection fraction (HFpEF) in order to characterize mechanisms of disease and identify therapeutic targets. Define sub-phenotypes of HFpEF by integrating existing phenotypic data on HFpEF subjects and controls from NIH cohorts and trials. Understand mechanisms of disease by integrating existing omics data across cohorts, including TOPMed, and generating new omics data. Investigate sub-phenotypes of HFpEF through deep phenotyping of a new cohort of recently diagnosed HFpEF subjects and controls. Identify and validate biologic targets through multi-omics evaluation of blood, urine, tissue.

RFA-HL-21-015 HeartShare: Next-Generation Phenomics to Define Heart Failure Subtypes (U01 Clinical Trial Not Allowed) RFA-HL-21-016HeartShare: Next Generation Phenomics to Define Heart Failure Subtypes and Treatment Targets Data Translation Center (U54 Clinical Trial Not Allowed)

Rising to the Public Health Challenge of COVID-19: The Community-Engaged Research Imperative

HEART

• Cardiovascular Complications

LUNG

• Acute Respiratory Distress Syndrome

(ARDS)

• Acute Respiratory Failure

BLOOD

• COVID-19–Associated Coagulopathy (CAC)

SLEEP

• Sleep Quality Impact on Complications

COVID-19 Cases in the U.S. as

• f October 20, 2020

Total Cases

<14K <39K <347K <163K <90K <867K 23

CDC COVID Data Tracker

Full Court Press Framework Addressing Near and Long-Term Impact of COVID-19

HOSPITAL PREVENTION ASYMPTOMATIC SYMPTOMATIC ER ICU RECOVERY RECOVERED

Goals

Reduce case severity/fatality, speed recovery

Host-Directed Therapeutics Clinical Trials

Understand short- and long-term trajectory Enable risk stratification, precision interventions Identify biomarkers and therapeutic targets Target populations most severely affected

Observational/Longitudinal Studies Data Resources and Platforms Community-Engaged Research

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Translational/Pre-Clinical Studies

NHLBI Clinical Research Portfolio: Therapeutic Targets Across the Clinical Course of COVID-19

ACTIV – 4B ACTIV – 4C

Pre-hospital Outpatient Post-hospital Convalescent Patients Hospitalized Patients (+/- ventilatory support)

ACTIV – 4A Patient Populations

Host-Directed Therapeutics Clinical Trials & Case Registries

C3P0 – Convalescent Plasma Anti- Thrombotic Passive Immunity Anti- Inflammatory COLOCORONA Colchicine ORCHID Hydroxychloroquine* (closed) Observational Studies

HOSPITAL PREVENTION ASYMPTOMATIC SYMPTOMATIC ER ICU RECOVERY RECOVERED

Understand disease pathobiology and long-term outcomes Assess blood safety and sero-surveillance *Trial ended in June 2020 following 4th DSMB determined drug unlikely to be beneficial to Hospitalized COVID-19 patients 25 ACTIV – 3 Monoclonal Antibodies

“Collaborating Network of Networks for Evaluating COVID-19 and Therapeutic Strategies”

• Comprehensive, expandable platform

linking trial network, registries and cohorts

• Leveraging existing assets, data and

studies

• Facilitating case finding, clinical trial

accrual, longitudinal studies, and community engagement

Collective Response to a Global Pandemic: Leveraging NHLBI Resources Through CONNECTS

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Advancing Comprehensive Understanding of Multisystem Inflammatory Syndrome in Children with COVID-19 (MIS-C)

MIS-C COHORT STUDIES Goal: Clinical and biological outcomes of MIS-C LONG-TERM FOLLOW UP Goal: Long-term whole-child effects of MIS-C PEDIATRIC COHORT Goal: SARS-CoV-2 spectrum of illness

Trans-NIH effort leveraging CARES Act funding and robust cloud-based data sharing

Coronary Aneurysms

MIS-C Cases in the U.S.

• >1,000 cases in U.S.
• >70% cases in children who are

Hispanic or Black

• 80% required ICU and Cardiovascular

involvement also seen in 80%

• Launched long-term observational

study (MUSIC) 9/30/20 - Clinical- physio-molecular characterization and follow-up for 5 yrs.

https://www.cdc.gov/mis-c/cases/index.html Feldstein et al. NEJM. 2020

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Impact of COVID-19 Across the U.S.: Disproportionately Affecting Communities of Color

Millett GA, et al. Annals of Epidemiology, 2020. https://ehe.amfar.org/

Disparities in case rates and risk of hospitalization and death from COVID-19 in minority communities

CDC COVIDView https://www.cdc.gov/coronavirus/2019-ncov/covid-data/

386.6 376.9 376.3 113.8 85.9 50 100 150 200 250 300 350 400 450

Hispanic or Latino Non-Hispanic American Indian or Alaska Native Non-Hispanic Black Non-Hispanic Asian or Pacific Islander Non-Hispanic White

Age-Adjusted COVID-19 Hosp. Rates from March 1-October 10

Counties with above average Black pops. 28 All other counties Counties with above average Latinx pops. All other counties

COVID-19 Cases by County (as of 10/15)

200 288K

Reducing the Burden of COVID-19 on Our Hardest-Hit Communities Through Engagement

Community Engagement Alliance Against COVID-19 Disparities (CEAL)

• Community-engaged research and
• utreach focused on COVID-19

awareness and education

• Addressing misinformation and

mistrust

• Promoting and facilitating inclusion of

diverse racial and ethnic populations in clinical trials

• Targeting populations

disproportionately affected by the pandemic 11 states identified as part of the alliance

Millett GA, et al. Annals of Epidemiology, 2020. https://ehe.amfar.org/

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NIH Community Engagement Alliance (CEAL) Against COVID-19 Disparities

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Trans-NIH initiative leading outreach, engagement and inclusive participation efforts in ethnic and racial minority communities disproportionately affected by the COVID-19 pandemic

Address Misinformation within Communities

• f Color

Foster an Understanding and Trust in Science Establish Partnerships within the Community Accelerate Inclusive Participation and Uptake of Beneficial Treatments

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Creating Partnerships that Share Trustworthy Information

Work with trusted messengers within communities Create mechanisms and tools to support community-engaged research “Recruiting Black volunteers for vaccine trials during a period of severe mistrust of the federal government and heightened awareness of racial injustice is a formidable task.”

'I Won't Be Used as a Guinea Pig for White People,' The New York Times, October 7, 2020

CEAL Teams: Addressing the adverse impact of misinformation and distrust in COVID-19 research

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Resilience: A working definition

“Resilience is the ability of living systems to successfully maintain or return to homeostasis in response to physical, molecular, individual, social, societal, or environmental challenges or stresses.”

The Concept of Resilience

Current NHLBI Portfolio Landscape

‘30, 000 foot view’

Search terms: Resist ∙ Recover ∙ Withstand ∙ Re-adjust ∙ Adaptive ∙ Challenge ∙ Healthy- aging ∙ Resilience ∙ Elasticity ∙ Recovery ∙ Adaptability ∙ Positive psychology ∙ Psychological-resilience ∙ Physiologic-resilience ∙ Well-being ∙ Positive-deviants ∙ Adaptation ∙ Health-maintenance ∙ Coping ∙ Self-efficacy ∙ Mastery ∙ Collateral ∙ Restoration ∙ Reperfusion ∙ Susceptibility ∙ Resistance ∙ Neoangiogenesis ∙Vasculogenesis ∙ Revascularization, Immune response, lymphangiogenesis

Broad, complex, multi-dimensional, sometimes abstract

Resilience

Social Determinants

Hypertension related CVD Preventing Vascular Dementia Reducing Burden of Heart Failure CVH across Lifespan

Resilience Workshops

• Enhancing Resilience for Cardiovascular Health and Wellness, 2018
• https://www.nhlbi.nih.gov/events/2018/enhancing-resilience-cardiovascular-

health-and-wellness

• Exerkines in Health, Resilience and Diseases, 2020
• Discovery of exerkines is only beginning and more to be discovered
• Mechanisms of how exerkines work are largely unknown
• Better understanding of interorgan communication of exerkines in humans is

needed

• Data of the roles of genetics, gender, race, and ethnicity on effects of exerkines

is lacking

• Development in phenotypic measures and biomarkers for resilience in health

and disease state is warranted

• No guidance is currently available on how to best use large databases (i.e.

http://www.metamex.eu/) for future studies

Exploring the Role of Endothelial Cell Resilience in Cardiovascular Health and Disease

36

https://www.ahajournals.org/doi/abs/10.1161/ATVBAHA.120.314346

Gao & Galis, Oct 2020

Vascular Dementia: Where can we be in 10 years?

• What vascular pathologies

contribute to cognitive impairment or dementia? How?

• Noninvasive biomarkers

(including imaging tools) for early diagnosis of dementia

• When to intervene and

how? Who to treat? Can we bend the curve?

Adapted from https://www.alzsd.org/resources/other-dementias

From: Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial

• JAMA. 2019;321(6):553-561. doi:10.1001/jama.2018.21442

Workshop on future clinical trials to test promising mechanisms for reducing vascular contributions to cognitive impairment and dementia, November 2019

Purpose

• To identify compelling research opportunities for clinical trials to test single or combined

interventions for the primary and secondary prevention of vascular contributions to VCID. Summary of Discussions

• Presentations and discussions were centered around:
• What are the most important unanswered scientific questions from the current epidemiological studies and

recently completed trials that address VCID risk factors for the prevention of cognitive impairment and dementia?

• What questions are being answered by some of the ongoing trials, including the rrAD, U.S. POINTER, MIND,

and SMARRT trials?

• What is known about mechanisms of VCID that can inform VCID trials, and what are the opportunities to

address mechanistic hypotheses in future VCID trials?

• Several important challenges and research opportunities.
• In future trials of younger participants who are at lower risk for MCI and dementia, validated surrogate markers
• f MCI and dementia with good correlation to clinical outcomes would be useful trial endpoints. Although there

has been progress in developing validated biomarkers, currently there are limitations for their use as primary

• utcome measures in efficacy trials.
• In future trials involving high-risk participants, it may be useful to combine MCI and dementia endpoints.
• Continuous measures of cognitive function have been used in observational studies, but their utility in efficacy

trials has not yet been established.

https://www.nhlbi.nih.gov/events/2019/future-clinical-trials-test-promising-approaches-reducing-vascular-contributions

https://preventabletrial.org/home.cfm